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D. Bandah, S. Merin, E. Banin, D. Sharon; The Spectrum of NR2E3 Mutations in Israeli and Palestinian Patients With Hereditary Retinal Degenerative Diseases. Invest. Ophthalmol. Vis. Sci. 2008;49(13):452. doi: https://doi.org/.
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The NR2E3 gene encodes a nuclear receptor transcription factor that is involved in photoreceptor differentiation. NR2E3 mutations were shown to be associated with different clinical phenotypes including enhanced S-cone syndrome (ESCS), Goldmann-Favre syndrome, and clumped pigmentary retinal degeneration. Our purpose was to evaluate the involvement of NR2E3 in retinal degenerative diseases in the Israeli and Palestinian populations.
Israeli and Palestinian patients from 35 families with various autosomal recessive retinal degenerative diseases were recruited for the study. Clinical evaluation included a full ophthalmologic exam, assessment of refractive error, color vision testing, and full-field electroretinography (ERG). Haplotype analysis was performed by studying single nucleotide polymorphisms (SNPs) within the NR2E3 gene. A screen for mutations was performed by direct sequencing of PCR products.
We recruited six consanguineous Muslim families and two Jewish families with the clinical diagnosis of ESCS. Patients from these families manifested decreased visual acuity early in life and the characteristic ERG findings which include severe impairment of the rod response accompanied by atypical supernormal cone responses under both photopic and scotopic conditions. Clumped pigment was observed in the peripheral retina of some of these patients. In four of the six Muslim families, we identified a known homozygous NR2E3 mutation, c.119-2A>C (IVS1-2A>C). In the remaining two Muslim families, no NR2E3 mutations were identified. In the two Jewish families, compound heterozygous mutations were found: patient MOL0581-1 was a compound heterozygote for a known NR2E3 mutation (c.932G>A; R311Q) and a novel deletion (c.194-202del9bp); patient MOL0528-1 was a compound heterozygote for c.932G>A and a novel splice-site mutation, c.747+1G>C (IVS5+1G>C). To study the possible role of NR2E3 in the etiology of retinitis pigmentosa (RP), we performed a homozygosity analysis in 27 consanguineous families with a clinical diagnosis of autosomal recessive RP. The analysis revealed a homozygous mutation, c.932G>A, in one Muslim and one Jewish family. Interestingly, the ERG responses in these patients were compatible with RP and did not show the characteristic ESCS pattern.
Our results demonstrate the involvement of NR2E3 in both ESCS and autosomal recessive RP in our population. Genetic testing for ESCS in the Muslim population will be enhanced with our identification of a common NR2E3 mutation causing the disease in this population.
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